A Total Product System Concept - a case study of the smart (tm) automobile

Increasing demand from consumers plus EU legislation has raised awareness within the automotive production sector of the urgent need to reduce the environmental impacts from the three main stages in vehicle life – car manufacture, car use and end-of life vehicle processing. The paper reviews how the originator and manufacturer of the smart automobile has worked directly with its main system partners to address environmental issues in these three stages while optimizing performance across the parameters of commercial viability. This required the creation of strategic relationships within the supply chain. Overall, this innovative approach is viewed in the context of a total product system. The smart car highlights the following critical areas: use of modularity in product design and production facility layout; emphasis on partner participation from product creation to after-sales; and the use of highly customised build-to-order product system to 'green' the entire supply chain. In particular, the case study compares the process characteristics empoyed at the smart car factory, called 'smartville', with more traditional approaches to vehicle manufacture. It exmaines these issues in a preliminary attempt to establish the actual or potential reduction of environmental impact in the three stages of vehicle life, including the role of main suppliers in this process

Dog ownership and physical activity: A review of the evidence

Background: Dog walking is a strategy for increasing population levels of physical activity (PA). Numerous cross-sectional studies of the relationship between dog ownership and PA have been conducted. The purpose was to review studies comparing PA of dog owners (DO) to nondog owners (NDO), summarize the prevalence of dog walking, and provide recommendations for research. Methods: A review of published studies (1990-2010) examining DO and NDO PA and the prevalence of dog walking was conducted (N = 29). Studies estimating the relationship between dog ownership and PA were grouped to create a pointestimate using meta-analysis. Results: Most studies were conducted in the last 5 years, were cross-sectional, and sampled adults from Australia or the United States. Approximately 60% of DO walked their dog, with a median duration and frequency of 160 minutes/week and 4 walks/week, respectively. Meta-analysis showed DO engage in more walking and PA than NDO and the effect sizes are small to moderate (d = 0.26 and d = 0.16, respectively). Three studies provided evidence of a directional relationship between dog ownership and walking. Conclusions: Longitudinal and interventional studies would provide stronger causal evidence for the relationship between dog ownership and PA. Improved knowledge of factors associated with dog walking will guide intervention research

Perspectives in Global Helioseismology, and the Road Ahead

We review the impact of global helioseismology on key questions concerning the internal structure and dynamics of the Sun, and consider the exciting challenges the field faces as it enters a fourth decade of science exploitation. We do so with an eye on the past, looking at the perspectives global helioseismology offered in its earlier phases, in particular the mid-to-late 1970s and the 1980s. We look at how modern, higher-quality, longer datasets coupled with new developments in analysis, have altered, refined, and changed some of those perspectives, and opened others that were not previously available for study. We finish by discussing outstanding challenges and questions for the field.Comment: Invited review; to appear in Solar Physics (24 pages, 6 figures

Euclid : Impact of non-linear and baryonic feedback prescriptions on cosmological parameter estimation from weak lensing cosmic shear

Upcoming surveys will map the growth of large-scale structure with unprecented precision, improving our understanding of the dark sector of the Universe. Unfortunately, much of the cosmological information is encoded on small scales, where the clustering of dark matter and the effects of astrophysical feedback processes are not fully understood. This can bias the estimates of cosmological parameters, which we study here for a joint analysis of mock Euclid cosmic shear and Planck cosmic microwave background data. We use different implementations for the modelling of the signal on small scales and find that they result in significantly different predictions. Moreover, the different non-linear corrections lead to biased parameter estimates, especially when the analysis is extended into the highly non-linear regime, with the Hubble constant, H0, and the clustering amplitude, σ8, affected the most. Improvements in the modelling of non-linear scales will therefore be needed if we are to resolve the current tension with more and better data. For a given prescription for the non-linear power spectrum, using different corrections for baryon physics does not significantly impact the precision of Euclid, but neglecting these correction does lead to large biases in the cosmological parameters. In order to extract precise and unbiased constraints on cosmological parameters from Euclid cosmic shear data, it is therefore essential to improve the accuracy of the recipes that account for non-linear structure formation, as well as the modelling of the impact of astrophysical processes that redistribute the baryons.Upcoming surveys will map the growth of large-scale structure with unprecented precision, improving our understanding of the dark sector of the Universe. Unfortunately, much of the cosmological information is encoded on small scales, where the clustering of dark matter and the effects of astrophysical feedback processes are not fully understood. This can bias the estimates of cosmological parameters, which we study here for a joint analysis of mock Euclid cosmic shear and Planck cosmic microwave background data. We use different implementations for the modelling of the signal on small scales and find that they result in significantly different predictions. Moreover, the different non-linear corrections lead to biased parameter estimates, especially when the analysis is extended into the highly non-linear regime, with the Hubble constant, H-0, and the clustering amplitude, sigma (8), affected the most. Improvements in the modelling of non-linear scales will therefore be needed if we are to resolve the current tension with more and better data. For a given prescription for the non-linear power spectrum, using different corrections for baryon physics does not significantly impact the precision of Euclid, but neglecting these correction does lead to large biases in the cosmological parameters. In order to extract precise and unbiased constraints on cosmological parameters from Euclid cosmic shear data, it is therefore essential to improve the accuracy of the recipes that account for non-linear structure formation, as well as the modelling of the impact of astrophysical processes that redistribute the baryons.Peer reviewe

Engineered immunogens to elicit antibodies against conserved coronavirus epitopes

Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine

Genetic analyses of diverse populations improves discovery for complex traits

Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry1–3. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific4–10. Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations11,12. Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States—where minority populations have a disproportionately higher burden of chronic conditions13—the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities. © 2019, The Author(s), under exclusive licence to Springer Nature Limited

Euclid: fast two-point correlation function covariance through linear construction

Galaxie

KiDS and Euclid: Cosmological implications of a pseudo angular power spectrum analysis of KiDS-1000 cosmic shear tomography

Large scale structure and cosmolog

Euclid preparation. XV. Forecasting cosmological constraints for the Euclid and CMB joint analysis

Galaxie